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J Struct Biol. 2014 Mar;185(3):366-74. doi: 10.1016/j.jsb.2014.01.008. Epub 2014 Jan 25.

Structure of MST2 SARAH domain provides insights into its interaction with RAPL.

Author information

1
School of Life Sciences, Anhui University, Hefei, Anhui 230039, China.
2
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
3
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: zczhou@sibcb.ac.cn.
4
School of Life Sciences, Anhui University, Hefei, Anhui 230039, China. Electronic address: zhmin07@ustc.edu.

Erratum in

  • J Struct Biol. 2014 Apr;186(1):204. Hao, Qiao [corrected to Hao, Qian].

Abstract

The STE20 kinases MST1 and MST2 are key players in mammalian Hippo pathway. The SARAH domains of MST1/2 act as a platform to mediate homodimerization and hetero-interaction with a range of adaptors including RASSFs and Salvador, which also possess SARAH domains. Here, we determined the crystal structure of human MST2 SARAH domain, which forms an antiparallel homodimeric coiled coil. Structural comparison indicates that SARAH domains of different proteins may utilize a shared dimerization module to form homodimer or heterodimer. Structure-guided mutational study identified specific interface residues critical for MST2 homodimerization. MST2 mutations disrupting its homodimerization also impaired its hetero-interaction with RAPL (also named RASSF5 and NORE1), which is mediated by their SARAH domains. Further biochemical and cellular assays indicated that SARAH domain-mediated homodimerization and hetero-interaction with RAPL are required for full activation of MST2 and therefore apoptotic functions in T cells.

KEYWORDS:

Apoptosis; Coiled coil; MST2; RAPL/RASSF5/NORE1; SARAH domain

PMID:
24468289
DOI:
10.1016/j.jsb.2014.01.008
[Indexed for MEDLINE]
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